Miss Millie Mayhem (Eng Bulldog) - NEW Dx: Cushings PDH and AWFUL Calcinosis Cutis

[Sabre's Mum]

Hi and welcome to you and Miss Millie Mayhem,

I have been doing a little research to see what new information has come to fruition over the past couple of years with regards to calcinosis cutis.

What concerns me in Millie' case is that the ACTH test is normal. We had a wonderful flowchart link on interpreting the LDDS test but that link now no longer works so I can't remember where the LDDS results point to (I have always referred to this flowchart as it was just so wonderful and I never imprinted into my mind!).

I found this link for calcinosis cutis http://www.vetbook.org/wiki/dog/inde...lcinosis_cutis. Generally calcinosis cutis points directly to cushings syndrome. There have however been rare cases of calcinosis cutis which have been caused by other factors which Lori pointed out above.

With the management of calcinosis cutis you are on the right track.

I must admit I am a little perplexed with Millie's test results and the calcinosis cutis given that her ACTH is normal. However an ACTH stim may be normal in some cases of ADH .... which is why I wanted a good explanation of the interpretation of the LDDS test (which has disappeared unfortunately).

What other blood tests has Millie had and what were the abnormal values?

Angela

[labblab]

Hello and welcome from me! Thought I'd go ahead and throw my thoughts into the ring, too.

This is just my personal opinion, but I do believe that Millie's list of classic Cushing's symptoms, the calcinosis cutis, and the positive LDDS all "trump" the ACTH and point to a genuine Cushing's diagnosis. Even though the ACTH is less prone to "false positives" than is the LDDS, it is far more prone to "false negatives," especially for dogs having the adrenal form of the disease. So in a situation such as this, where Millie is so symptomatic but has turned up with a negative on the ACTH, the recommended protocol would indeed be to turn to the LDDS for further confirmation. The abundance of false negatives on the ACTH is probably the main reason why many specialists discount the ACTH as the initial Cushing's testing tool, although I do believe there are situations where the ACTH has a testing advantage (but I won't bore you with an explanation here).

On their own, Millie's LDDS results do not distinguish between the pituitary and adrenal forms of the disease. But her ultrasound is consistent with PDH since both adrenals were enlarged. So if it were me, I would feel as though your vets are making the right decision in pushing ahead with treatment given Millie's entire symptom and testing profile.

One quick question for you: you mention that she is also taking phenobarb. Does she have a seizure disorder? I will come back and add another reply about the phenobarb, but it may end up having an effect on the trilostane dosing down the road.

Marianne

[khockman]

Thank you to everyone! So - as to the question when was her last lepto vaccination - it was in 2009 before we moved. Just talked to the vet and they said they don't really push it anymore because there are so many strains of lepto ? As it relates to the phenobarb, she has been on it a while - 64.8 mg (on pill in morning one at night). She has what was diagnosed to be mild seizures (biting at the air, staring off into space, head tremor).

Back to the ACTH test and LDDS...with the LDDS, I was worried by the fact hat the baseline fell within normal as did the 4 hr and 8 hr (baseline:2.5, 4 hr: 2.4, 8 hr: 2.3 respectively)... The results indicated it is consistent with hyperadrenocorticism but further testing required to determine ADH or PDH (4 hr: >1.5 and >50% of baseline; 8 hr: >1.5 and >50% of baseline). I think the biggest thing was that she did not really supress at all?

All test results for everything are below:

Urinalysis: Sp. Gr. 10.18 (?), Color: lt. yellow, PH: 6.5, Protien:

Trace – Reading handwriting so hope I got this correct…no other values noted.

LDDS: Pre-Dex: 2.5 ug/dL, 4Hr: 2.4 ug/dL, 8Hr: 2.3 ug/dL – I thought it was strange her baseline was within the normal range, but both vets said that it can fluctuate through the day. Also thought since baseline was somewhat normal, I was surprised her calcinosis cutis was SO EXTREME.

Bacterial/Skin Test: I cannot decipher these results, but it was determined she had staph and strep infections.

Biopsy: Clinical Summary – Three week history of erosions, dorsal neck, spreading along the back. Lesions are surrounded by erythematous plaques. White irregular serpiginous plaques on lateral neck. Two punch biopsies of erythematous plaques and one of white plaque. History of allergic disease. Suspect calcinosis cutis. Skin scrapings negative. Cocci seen on cytology. Patient is PU/PD with increased appetite. Gross Description - One container labeled “Millie,” three specimens, six sections in one cassette. 3 skin punch biopsies, bisected and totally submitted as six sections in one cassette, specimens inked blue, yellow, unlinked identification of halves. Diagnosis – Skin biopsies, dorsal plaques: calcinosis cutis, multifocal. The epidermis is acanthotic and suffers multifocal edema and vacuolar degeneration. There is a thick layer of loose orthokeratotic keratin on skin surface. Somewhat cystic follicular keratosis with follicular casts is also evident. The dermis is becoming mineralized. This has incited a granulomatous response and fibrosis. There are also small fragments of mineralized bone in the affected tissue (SHOULD I BE CONCERNED ABOUT THIS…BONE IN TISSUE??). Comment – Clinical Diagnosis of Calcinosis Cutis is confirmed…

ACTH: Time 1: 3, Time 2: 4, Cortisol Sample 1: 2.1 ug/dL, Cortisol Sample 2: 8.5 ug/dL (I believe the vet said this test was inconclusive?)

Superchem: Just reporting “abnormal” – Albumin: 2.1 (LOW), A/G Ration: 0.7 (LOW), Alk Phosphatase: 1704 (HIGH – this seems off the charts to me…normal is 5-131 U/L), Magnesium: 1.4 (LOW), Potassium: 5.6 (HIGH)

CBC: Just reporting “abnormal” – Platelet Count: 595 (HIGH), Differential Neutrophils: 11097, 81% (HIGH)


P.S. - believe me I am all over the poor girl watching for signs for too low cortisol as I am a bit nervous.

[addy]

Hi and Welcome,

I cant help with the test results. I can give you a link to a case study of a dog with calcinosis cutis on his body and face. He did recover, it took six months. I dont want to scare you but rather give you hope. In this case study the dog is being treated with Lysodren but still developed the calcinosis cutis. I thought you might glean something from reading it even though you are using Trilostane.

http://veterinarymedicine.dvm360.com....jsp?id=659278

My Zoe has mild calcinosis cutis and other skin issues as well. Her skin issues go a lot worse before they got better because our specialist led me down the wrong road for nine months or more regarding her skin.

I know the administrators will be by to recheck your lab work.

Glad you found us.

[khockman]

Yes - you did give me hope! I quickly scanned through (of course analyzing the pics and my girl has same face issues but a little worse down the trunk - it is just awful) and am going to print and read. I know everyone said it is going to be a long haul, but I am ok with it as long as I feel there is hope and as long as I am doing everything possible to make her comfortable. How did your specialist lead you wrong? Right now I am using DMSO and an antibacterial mousse...

Mel also mentioned she used Sudocrem and someone is using Manuka Honey - going to look at both options as well.

[addy]

Mine discouraged me from frequent bathing, did not identify the mild bacteria and yeast though I repeatedly asked if she had it. She just did not know much about skin issues. Many dont here in the States. Ironically she recognized that and told me recently she was attending a conference in June and they had a class on 'Things Internal Medicine Specialists should know about Skin"

Read as much as you can, I cant stress it enough, even if you may not think you understand the articles or technical terms, somewhere down the road, the information may give you an "AHA" moment.

hugs

[labblab]

Me again! As far as Millie's baseline cortisol, your vets are right in saying that the baseline reading does not have any significance for making a Cushng's diagnosis on either the ACTH or LDDS. It is only the subsequent blood draws -- after the testing agents have been administered -- that determine the diagnosis.

Also, in the case of the LDDS, the "normal" reference range is entirely different for the subsequent blood draws than it is for the baseline reading. For most labs, the normal "cut-off" is somewhere around 1.4 or 1.5 ug/dl. This means that if the 8-hour result is greater than the cut-off point, the test result is "positive" for Cushing's. At that point, you take a look at the 4-hour result, as well, in seeing whether the test points the finger at the pituitary rather than the adrenal form. Here's a link that explains the test interpretation in far more detail:

http://veterinarymedicine.dvm360.com.../detail/580093

And thanks for the info about the phenobarb. I'll come back and add some more about that in a little while.

Mariannne

[labblab]

Me again, again.

OK, first a question: I just want to double-check that second number for the ACTH test result. You've written 8.5 ug/dl, and I'm just wondering whether it might instead have been 18.5 ug/dl? That higher number still wouldn't have been conclusive for Cushing's, but it would seem less surprising than the 8.5 which does not reflect any elevation at all.

But regardless, switching to the phenobarb, I have a non-Cushpup who is treated with phenobarb for grand mal seizures. Boy, I have surely discovered that phenobarb interacts with a whole bunch of other drugs! It can be a real pain, sometimes, to find alternatives that don't interfere or compete with it. Phenobarb is known to interact with mitotane (brandname is Lysodren), which is the other commonly prescribed Cushing's med. And while phenobarb is not listed as actively interacting with trilostane, apparently some dosing alterations may be recommended along the way. Here's a related reply that I posted to another member some time ago:

OK, I just spoke with one of Dechra's technical reps, and what he told me pretty much coincides with what you were already thinking. Even though there is no documented interaction between trilostane and phenobarb (he is unaware of any clinical trials that specifically addressed that drug combination), dogs who are being treated with both drugs need to be monotored very diligently both in terms of liver function and also trilostane efficacy. He is aware of dogs that are currently being treated with both drugs, and no particular problems have surfaced thus far. But theoretically, phenobarb's effect on the liver could alter the way in which trilostane is metabolized by any given dog, leading to the potential for trilostane overdosing in the absence of appropriate dosing adjustments.

I believe there has been some discussion that perhaps potassium or sodium bromide might be a better "match" with trilostane because the bromides do not have the same effect on the liver as does phenobarb. But I've recently been reading that the bromides are linked with a higher incidence of pancreatitis, and I think that Cushpups may already be more vulnerable to pancreatitis without adding in another complicating factor. So I don't know that there is a perfect answer in terms of drug preferability.

However, the bottom line is that I'd encourage your vets to call a technical rep at Dechra (manufacturer of brandname Vetoryl) in order to see what their most current advice is re: dosing recommendations for dogs taking phenobarb. That way, you'll know you're getting the most up-to-date advice in this regard.

Marianne

[khockman]

Thanks Marianne…you can offer advice and replies again and again and again! Yes I was correct in stating 8.5 (reference range was 8-17) it did state as you have mentioned, for HAC post results would be greater than 20. Perhaps this is why vet said inconclusive given all other symptoms? I appreciate your comments and information on phenobarb…I will be asking my vet questions regarding that and making sure a call is placed to Dechra

Everyone is offering such good insight and I am doing all I can to read, read and read some more. I would not call myself a dummy, but until all of this, if you asked me what the pituitary does, where the adrenal glands are and what cortisol is, I would have looked at you like a deer in headlights (I know I learned all of this years ago, but have some reason managed to bury it away)!

Positive note is that I think I am still capable of learning

[labblab]

And obviously you are doing a great job re: all that new learning!!!

One more thought does occur to me. I know that increased thirst, urination, and lethargy can also be side effects of phenobarb. Do you think there was any relationship in the timing of the symptom onset for Millie? When we started our non-Cushpup on phenobarb, she really looked and acted just like my pre-treatment Cushing's dog for a while. Fortunately, for us, those symptoms dropped away once she was stabilized on the phenobarb. But it does cross my mind to ask about that since we are basing Millie's diagnosis partly on those symptoms being part of her profile.